Extended treatment with oral alitretinoin for patients with chronic hand eczema not fully responding to initial treatment.

BACKGROUND: In a previous large trial (Benefit of Alitretinoin in Chronic Hand Eczema; BACH), 47.7% of patients with severe chronic hand eczema (CHE) who received alitretinoin 30 mg achieved 'clear' or 'almost clear' hands during the initial 24-week treatment course. OBJECTIVES: The current open-label trial was designed to study extended treatment with a further 12- to 24-week course of oral alitretinoin 30 mg in patients who did not fully respond to initial treatment in the BACH study. METHODS: At the end of the BACH study, patients whose eczema was rated 'mild', 'moderate' or 'severe' according to the Physician's Global Assessment (PGA) were eligible for a 24-week, open-label, multicentre study. Patients (n=243) received 30 mg of alitretinoin once daily, irrespective of previous treatment in BACH; either alitretinoin 30 mg, alitretinoin 10 mg or placebo. RESULTS: By the end of the follow-on study, the PGA response rate to the subsequent course of alitretinoin 30 mg was 50% and 39% in patients treated previously in BACH with 10 or 30 mg per day, respectively, and 51% in patients who previously received placebo in BACH. Alitretinoin was well tolerated, and no significant late-arising toxicities were seen. CONCLUSIONS: For a considerable number of patients with CHE who did not fully respond after an initial 24-week treatment period, a switch from either placebo to the active compound at 30 mg or from the lower to the higher dose, or treatment prolongation at the higher dose could be beneficial. Alitretinoin remains well tolerated for overall treatment durations of up to 48 weeks.

History of pediatric regional anesthesia.

The history of local and regional anesthesia began with the discovery of the local anesthetic properties of cocaine in 1884. Shortly afterwards nerve blocks were being attempted for surgical anesthesia. Bier introduced spinal anesthesia in 1898, two of his first six patients being children. Spinal anesthesia became more widely used with the advent of better local anesthetics, stovaine and procaine in 1904-1905. Caudals and epidurals came into use in children much later. In the early years these blocks were performed by surgeons but as other doctors began to give anaesthetics the specialty of anesthesia evolved and these practitioners gradually took over this role. Specific reports of their use in children have increased as pediatric anesthesia has developed. Spinals and other local techniques had periods of greater and lesser use and have not been universally employed. Initial loss of popularity seemed to relate to improvements in general anaesthesia. The advent of lignocaine (1943) and longer acting bupivacaine (1963) and increasing concern about postoperative analgesia in the 1970-1980s, contributed to the increased use of blocks.

The early development of pediatric intensive care.

The polio epidemic in Copenhagen in 1952 was a significant stimulus to the development of Intensive Care. Eighty-five percent of the patients with respiratory involvement died despite the use of Cuirass negative pressure ventilators. After some controversy Ibsen, an anesthetist, was consulted. He found that many patients were dying with CO(2) retention. He advocated tracheostomy, suction, and ventilation. Owing to the lack of positive pressure ventilators, this was undertaken by students who contributed 167,000 h of hand ventilation. The mortality decreased to 25%. Anesthetists, having special experience with ventilation, became the leaders in the field as Intensive Care developed.

Neuroradiology investigations before scanning.

Coaxial tomography (CT) and magnetic resonance imaging (MRI) scans are so much part of neurological investigation these days and provide such detailed information that even thorough neurological clinical examination may be neglected. The investigations in common use forty years ago were pneumoencephalography, ventriculography in babies with hydrocephalus, and carotid angiography with the injection of X-ray contrast to outline the arteries.

Pediatric anesthetic meetings and conferences.

In 1984, David Steward (in Figure 1, front row) and Seizo Iwai (Figure 2) organized a meeting of pediatric anesthetists in Manila during the World Congress of Anesthesiologists. Following the meeting, there was a dinner at which John Zorab, then Secretary of the World Federation of Societies of Anaesthesiologists (WFSA), told the audience that if they wanted to set up a Paediatric Committee in the WFSA, they should request to do so immediately. A show of hands at this informal occasion showed a majority but not unanimous approval (because no aims and objectives had been defined for the committee). It was established at the WFSA Executive meeting the next day. Eventually, a multiauthored WFSA handbook on Pediatric Anesthesia, initiated by David Steward and finalized by Anneke Meursing, was produced some years later.

Early experiences of vasodilators and hypotensive anesthesia in children.

The physiological application of OHMS LAW explains the basis of hypotensive anesthesia. V = IR translates into: Pressure = Flow × Resistance or Blood pressure = Cardiac Output × Peripheral Resistance. If peripheral resistance is reduced by a vasodilator such as sodium nitroprusside (a short acting, vascular smooth muscle relaxant) or phenoxybenzamine (a long acting α adrenoreceptor antagonist), blood pressure will fall and vasoconstriction and bleeding will be reduced. A less desirable alternative to lowering blood pressure could be to reduce cardiac output by suppressing myocardial contractility using a ß(1) adrenoceptor antagonist or an inhalational agent such as isoflurane.

Neonatal revolution - the introduction of PEEP.

Fifty years ago, a baby born at 24-26 weeks was not considered viable. It was a tragedy for the mother having carried it for so long. I witnessed such an event as a student. The scourge of premature deliveries was the lack of surfactant in many tiny babies. In general, if a premature infant with hyaline membrane disease, as it was called respiratory distress syndrome (RDS), could not maintain a pO(2) above 60 mmHg in 100% oxygen, it was not expected to survive. In late 1969, two babies with suspected RDS came to ICU and were treated by the author with the buffer (tris hydroxyl amino methane, [THAM] which reduced both metabolic and respiratory acidosis and did not contain sodium) and an isoprenaline infusion (ß(1) stimulant and pulmonary vasodilator). The X-ray appearances of RDS disappeared. Unfortunately, one died of portal vein thrombosis because the drugs were administered by umbilical catheter, which were commonly used at the time. The other one recovered but the physicians then said the diagnosis must have been wrong!

Digby Leigh.

Digby Leigh was a pioneer of Canadian pediatric anesthesia. He was an outstanding man - once met, never forgotten. My only contact with him was at the First Paediatric Anaesthesia Workshop at HSC in Toronto organized by Alan Conn in 1964. He chaired a panel with Jackson Rees from Liverpool and Bob Cope, a gentlemanly senior anesthetist at the Hospital for Sick Children, Great Ormond Street in London. The introduction was followed by 'We are all enemies,' a sure start for a vigorous debate. Digby Leigh was born in Jersey, grew up in British Columbia where he attended the University of British Columbia. He moved to Montreal to attend McGill University because there was no medical school in Vancouver. He graduated in 1932 and, like many others, began surgical training at Montreal Children's before Wesley Bourne, Chief of Anaesthesia, persuaded him to change to Anaesthesia. He went to Madison, Wisconsin, and trained with one of the great pioneer teachers, Ralph Waters, for 3 years.

Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema.

BACKGROUND: Patients with severe chronic hand eczema (CHE) often respond to therapy with oral alitretinoin (9-cis retinoic acid). However, the efficacy of alitretinoin after disease relapse has not been demonstrated. OBJECTIVES: To assess the efficacy and safety of a second course of oral alitretinoin in patients with severe CHE who relapsed after achieving 'clear' or 'almost clear' hands following a previous course of alitretinoin. METHODS: The double-blind study included 117 patients with CHE who had responded to therapy in an earlier clinical trial and subsequently relapsed. Patients were randomized to receive their previous treatment or placebo. Treatment was alitretinoin 30 mg or 10 mg or placebo given once daily for 12-24 weeks. Response was defined as an overall Physician's Global Assessment rating of 'clear' or 'almost clear' hands at the end of therapy. RESULTS: Response rates were 80% in patients retreated with 30 mg alitretinoin compared with 8% for placebo (P < 0.001). In patients retreated with 10 mg alitretinoin response rates were 48%, compared with 10% in the placebo group. Alitretinoin was well tolerated. Adverse reactions comprised typical retinoid class effects, and no late-arising side-effects were observed during this second course of treatment. CONCLUSIONS: The majority of patients with CHE who previously achieved 'clear' or 'almost clear' hands following treatment with alitretinoin 30 mg per day also responded to a second course of treatment. Retreatment was well tolerated. Intermittent treatment with alitretinoin is suitable for the long-term management of CHE.